Anxiety has been pointed to as the key symptom of the cocaine withdrawal syndrome in human addicts and is considered to be one of the most important factors in precipitating relapse to chronic cocaine abuse (Sarnyai et al., 1995). Corticotropin releasing factor has been implicated in mediating the "anxiety-like" behavior that is observed during the initial phase of cocaine abstinence (Sarnyai et al., 1995) and stress induced relapse to cocaine-conditioned place preference (Lu et al., 2001). In addition, it has been previously determined that chronic cocaine self-administration upregulates norepinephrine transporter in the bed nucleus of the stria terminalis (BNST), an area rich in noradrenergic fibers, indicating that the BNST may play a role in cocaine withdrawal and the stress-related reinstatement of cocaine self-administration following cocaine abstinence (Macey et al., 2003). The guiding hypothesis for this proposal is that the "anxiety-like" behavior that is observed during cocaine abstinence (Sarnyai et al., 1995) and the stress-induced relapse to cocaine use (Lu et al., 2001) may be mediated by the effects of cocaine on noradrenergic circuits originating from brainstem nuclei (e.g. locus coeruleus) to the amygdala.